Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing intestinal absorptive surface by mucosal regeneration on serosal patched intestinal defects is a potential surgical treatment for the short bowel syndrome. We previously found in long-term studies that serosal patching in dogs undergoing 75% enterectomy was deleterious to intestinal adaptation and absorption. Our aim was to evaluate the effect of serosal patching on the early morphologic and functional changes in postresectional adaptation and to examine the role of polyamine metabolic pathways in this process. Five unoperated New Zealand white rabbits (GP I) served as controls. Twelve other rabbits underwent either 50% distal enterectomy alone (GP II) or simultaneously had two 2 x 5-cm full-thickness ileal defects patched with adjacent cecal serosa (GP III). Animals in GP II gained an average of 7.2 +/- 5.3% body weight, whereas GP III animals lost 5.6 +/- 9.0% body weight (P less than 0.05). Intestinal remnant length was significantly less in GP III 3 weeks postoperatively (66 +/- 11 vs 85 +/- 8 cm, P less than 0.05) as was mucosal protein content (4.1 +/- 1.8% vs 6.2 +/- 1.9%) but villus height was similar in GPs II and III (505 +/- 131 vs 508 +/- 110 microns). In vitro mucosal function was similar in all three groups. Crypt cell production rate was significantly lower while ornithine decarboxylase and diamine oxidase activity were higher in GP III compared to GP II. However, polyamine levels were similar in all three groups. Serosal patching impairs intestinal adaptation following massive enterectomy. This is due in part to a decrease in proliferative activity which is not directly related to altered polyamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serosal patching impairs intestinal adaptation following enterectomy. 174 Sep 32

Patching intestinal defects with adjacent serosal surfaces results in the growth of new intestinal mucosa. Since polyamine biosynthesis is associated with cellular growth and differentiation, it may be important in this regenerative process. Our aim was to determine the effect of eflorithine (difluoromethylornithine), a specific inhibitor of polyamine synthesis, on intestinal regeneration. Forty-eight New Zealand white rabbits had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. One half of the animals took 2% eflorithine in drinking water postoperatively. Six animals in each group were killed 7, 14, 21, and 28 days after patching. There was no significant difference in neomucosal growth at any time. Villous height, disaccharidase activity, and crypt cell production were significantly lower in the eflorithine-treated animals. Eflorithine-treated animals had significantly lower ornithine decarboxylase activity and polyamine levels. Despite the inhibitory effect of eflorithine on polyamine synthesis and proliferative activity, epithelialization and contraction of the patched defect were not affected. These findings suggest that polyamine synthesis is important in proliferation and differentiation of cells in the neomucosa but does not influence cell migration in intestinal regeneration.
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PMID:Effect of eflorithine on intestinal regeneration. 249 77

Urogastrone (UG) administered subcutaneously increases the rate of intestinal regeneration (neomucosal growth) on patched intestinal defects. Our purpose was to determine the optimal route of delivery of UG for intestinal regeneration. In 22 New Zealand white rabbits (2.1 to 3.4 kg) 2 X 5 cm ileal defects were patched with adjacent cecal serosal surface. Group I (n = 6) served as controls. Group II (n = 5), group III (n = 6), and group IV (n = 5) received UG, 1.5 micrograms/kg/hr, intravenously, subcutaneously, and intraluminally via miniosmotic pumps. Neomucosal growth was assessed 7 days after patching. Serum UG levels were detectable in only the intravenous group. Coverage of the patched defect and neomucosal area was significantly greater and contraction of the defect less in the groups receiving UG (p less than 0.05). Neomucosal area was highest in the intravenous group (286 +/- 16 mm2), intermediate in groups III and IV (236 +/- 19 and 215 +/- 20 mm2), and lowest in the control group (152 +/- 17 mm2; p less than 0.05). Sucrase and maltase activities were significantly higher in the intravenous group. Crypt cell production rate and ornithine decarboxylase activity were greater in the UG-treated animals. UG stimulated intestinal regeneration by all routes of delivery. The intravenous route had the greatest effect and was associated with the highest serum levels of UG. These findings have implications for the mechanism of the trophic effect of UG on the intestinal epithelium.
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PMID:The effect of the route of delivery of urogastrone on intestinal regeneration. 250 Jul 25

Intestinal resection stimulates proliferative activity in the intestinal remnant. The aim of this study was to determine the influence of intestinal resection on the growth of intestinal neomucosa. Forty-eight New Zealand white rabbits had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. Group I (n = 24) served as controls. Group II (n = 24) underwent simultaneous 50% enterectomy. Neomucosal coverage was significantly greater in Group II at 1 week (36 +/- 11% vs 67 +/- 9%, P less than 0.05) and 2 weeks (94 +/- 2% vs 99 +/- 1%, P less than 0.05), but was similar at 3 and 4 weeks. There was significantly more neomucosa at 1 week in the animals that underwent resection (134 +/- 55 mm2 vs 199 +/- 54 mm2, P less than 0.05). Degree of patch contraction, glucose uptake, and disaccharidase activities were similar in each group. Ornithine decarboxylase activity and crypt cell production rate were significantly greater at 1 week in the animals that underwent resection. Intestinal resection results in an early increase in neomucosal growth and increased proliferative activity. Since contraction of the patches occurs to a similar extent in both groups, the total amount of neomucosa was not increased. Thus, performing patching at the time of resection is not necessary for optimal growth.
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PMID:The influence of intestinal resection on the growth of intestinal neomucosa. 270 28

Urogastrone (UG) stimulates the growth of intestinal neomucosa on patched intestinal defects. This effect may be dependent on increased polyamine biosynthesis. The aim of this study was to determine if difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis, would inhibit urogastrone stimulation of neomucosal growth. Twenty-four New Zealand white rabbits (2.1-2.9 kg) had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. Group I (n = 6) served as controls. Group II (n = 6) received UG 1.5 micrograms/kg/hr subcutaneously. Group III (n = 6) took 2% DFMO orally. Group IV (n = 6) received the same doses of UG and DFMO simultaneously. Animals were sacrificed 7 days after patching to assess neomucosal growth. Urogastrone infusion resulted in significantly greater neomucosal coverage (54 +/- 4%) and neomucosal surface area (236 +/- 18 mm2) in the Group II animals. Neomucosal coverage and contraction of the intestinal defects and neomucosal surface area were similar in the other three groups. Crypt cell production rate (15.5 +/- 2.0 cells/hr) and disaccharidase activity were also significantly greater in Group II than in the other groups. DFMO alone (Group III) resulted in a significantly lower ornithine decarboxylase (ODC) activity, polyamine content, and crypt cell production rate. Group IV animals had lower ODC activity but not lower polyamine content or crypt cell production rate. UG resulted in a significant increase in neomucosal growth. DFMO prevented this stimulatory effect and inhibited ornithine decarboxylase activity. The stimulation of neomucosal growth by UG is dependent, at least in part, on increased polyamine biosynthesis.
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PMID:Difluoromethylornithine inhibits urogastrone stimulation of neomucosal growth. 313 90

We investigated the antiviral activity of olive leaf extract (OLE) preparations standardized by liquid chromatography-coupled mass spectrometry (LC-MS) against HIV-1 infection and replication. We find that OLE inhibits acute infection and cell-to-cell transmission of HIV-1 as assayed by syncytia formation using uninfected MT2 cells co-cultured with HIV-1-infected H9 T lymphocytes. OLE also inhibits HIV-1 replication as assayed by p24 expression in infected H9 cells. These anti-HIV effects of OLE are dose dependent, with EC(50)s of around 0.2 microg/ml. In the effective dose range, no cytotoxicity on uninfected target cells was detected. The therapeutic index of OLE is above 5000. To identify viral and host targets for OLE, we characterized gene expression profiles associated with HIV-1 infection and OLE treatment using cDNA microarrays. HIV-1 infection modulates the expression patterns of cellular genes involved in apoptosis, stress, cytokine, protein kinase C, and hedgehog signaling. HIV-1 infection up-regulates the expression of the heat-shock proteins hsp27 and hsp90, the DNA damage inducible transcript 1 gadd45, the p53-binding protein mdm2, and the hedgehog signal protein patched 1, while it down-regulates the expression of the anti-apoptotic BCL2-associated X protein Bax. Treatment with OLE reverses many of these HIV-1 infection-associated changes. Treatment of HIV-1-infected cells with OLE also up-regulates the expression of the apoptosis inhibitor proteins IAP1 and 2, as well as the calcium and protein kinase C pathway signaling molecules IL-2, IL-2Ralpha, and ornithine decarboxylase ODC1.
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PMID:Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. 1287 15

Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in the polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention of basal cell carcinomas (BCCs), the majority of which have mutations in the tumor-suppressor gene known as patched (PTCH). To assess this possibility, we first overexpressed ODC in the skin of Ptch1+/- mice using a keratin 6 (K6) promoter that directs constitutive ODC expression in the outer root sheath of the hair follicle. UVB irradiation of these mice accelerated induction of BCCs as compared with their Ptch1+/- littermates. To further verify the role of ODC in BCC tumorigenesis, we used an antizyme (AZ) approach to inhibit ODC activity in the Ptch1+/- mice. Ptch1+/- mice with AZ overexpression driven by the K6 promoter were resistant to the induction of BCCs by UVB. Furthermore, oral administration of the suicidal ODC inhibitor alpha-difluoromethylornithine reduced UVB-induced BCCs in Ptch1+/- mice. These results demonstrate the crucial importance of ODC for the induction of BCCs and indicate that chemopreventive strategies directed at inhibiting this enzyme may be useful in reducing BCCs in human populations.
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PMID:Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/- mice. 1506 19